Objectives: Thyroid autoimmunity is a major cause for hypothyroidism. We describe thyroid auto-antibodies in patients with various nosological subtypes of hypothyroidism identified in a population study. Design: Population-based follow-up study identifying all new cases of hypothyroidism in an open cohort. Methods: We established a monitoring system, and identified all new cases with primary overt hypothyroidism (n = 685) in a 4 year period in a well-defined population cohort (2,027,208 person-years of observation). Patients were sub-classified into: spontaneous hypothyroidism, presumably of autoimmune origin ( n 578); non-spontaneous hypothyroidism ( associated with medication, delivery, neck-irradiation or subacute thyroiditis, n 97); and congenital hypothyroidism ( n 10). A total of 186 adult patients (61% of those invited) underwent thyroid ultrasonography and measurements of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb). Results: In spontaneously hypothyroid patients: > 99% were antibody-positive ( TPOAb or TgAb), TPOAb were more often measurable than TgAb (95.9 vs. 80.7%, p, <0.001). A statistically significant but modest correlation was observed between the two antibodies (Pearson's r(2) = 0.11, p <0.001). In a multivariate regression model both TPOAb and TgAb were positively associated with thyroid enlargement ( p, 0.001), whereas no association was found with sex, age, iodine deficiency level or serum TSH level. We found no differences in patient characteristics between those who mainly developed TPOAb vs. those who preferentially harboured TgAb. Conclusions: Autoimmunity played a dominant role in practically all patients classified as spontaneously hypothyroid. Thyroid enlargement was associated with high levels of TPOAb and TgAb. We found no clue to why some spontaneously hypothyroid patients predominantly developed TPOAb whereas others mainly generated TgAb.